PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

Is additive manufacturing a magic bullet to resupply lacking PPE? Producing respirators and face shields during COVID-19 pandemic: A systematic review.

Coronavirus Disease 2019 (COVID-19) pandemic caused an increase in the demand for personal protective equipment (PPE) and disruptions in production chains, resulting in an acute shortage of PPE. A possible solution to this problem was additive manufacturing (AM) technology - allowing for a quick start of the production of PPE and potentially able to meet the demand until the production is restored. In addition, AM allows for the production of PPE prototypes with potentially greater comfort of use or degree of protection. In order to assess the production of PPE in AM during the COVID-19 pandemic, previously published articles in this field were analyzed. After analyzing abstracts and full texts, 30 original works were selected from the initially collected 487 articles. Based on the analyzed literature, it was found that there are not enough studies comparing traditional and AM PPE as well as not enough comparisons of the different types of AM PPE with each other. In many cases, researchers focused only on the subjective assessment of the comfort of using PPE, without assessing their effectiveness in preventing infections. Despite that, AM has a great potential to quickly produce lacking PPE. Respirators and shields made by AM were rated by the vast majority of users as comfortable to wear. Some of the respirators could be adapted to a specific user, by designing on the basis of a face scan or after warming up the finished print and modeling the shape.